Reversible inactivation of the insular cortex by tetrodotoxin produces retrograde and anterograde amnesia for inhibitory avoidance and spatial learning.

Tetrodotoxin (TTX; a voltage-sensitive sodium channel blocker) was microinjected bilaterally into the insular (IC), frontal (FC), or parietal (PC) cortex or the ventral caudate nucleus of rats either before or after they were trained in an inhibitory avoidance task. When administered either before or after training, injections of TTX into the IC impaired performance on a 48-hr retention test. Injections of TTX into the PC also impaired retention when administered before training. One week later, rats with cannulae in the IC, FC, and PC received microinjections of TTX either before or after training in a water maze (Morris) spatial learning task and retention was tested 24 hr later. TTX impaired retention when administered to the IC either before or after training. These findings indicate that a functionally intact IC during and after training in these tasks appears to be essential for the storage of long-term memory.